Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study.

BACKGROUND: Type 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation. METHODS: We analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18-36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors. RESULTS: After discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001). CONCLUSIONS: A high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Diagnostic Ability and Safety of Repeated Pancreatic Juice Cytology Using an Endoscopic Nasopancreatic Drainage Catheter for Pancreatic Ductal Adenocarcinoma: A Multicenter Prospective Study.

Pathological examination is essential for the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Moreover, a reliable pathological diagnosis is extremely important for improving prognosis, especially in early-stage PDAC. This study prospectively evaluated the usefulness of repeated pancreatic juice cytology (PJC) using an endoscopic nasopancreatic drainage (ENPD) catheter for the diagnosis of PDAC. We enrolled 82 patients suspected of having resectable PDAC, based on imaging studies, and judged the necessity for cytology. The diagnostic yield of up to six repeated PJCs and the incidence of complications, such as pancreatitis, was evaluated. A total of 60 patients were diagnosed with PDAC. The overall sensitivity and specificity were 46.7% and 95.5%, respectively. The cumulative positivity rate increased with the number of sampling sessions, reaching 58.3% in the sixth session. The sensitivity was significantly higher in the pancreatic head than in the pancreatic tail (p = 0.043). Additionally, it was 100% in four patients with a tumor size ≤10 mm. Pancreatitis occurred in six patients (7.3%), all of whom were treated conservatively. In the diagnosis of PDAC, repeated PJC using an ENPD catheter revealed a cumulative effect of sensitivity up to six times and an excellent diagnostic yield for small PDAC.

Duodenal diverticula perforation caused by an impacted bezoar successfully treated by endoscopic drainage and lithotripsy: A case report and literature review.

Duodenal diverticula perforation due to an impacted bezoar is a rare disease. Surgical treatment is associated with high rates of complications and mortality; therefore, treatment strategies must be carefully decided. Endoscopic treatment offers significant benefits to patients over surgery.

Clinical Analysis of Early-Stage Pancreatic Cancer and Proposal for a New Diagnostic Algorithm: A Multicenter Observational Study.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC; especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed.

[A Case of Resected Esophageal Endocrine Cell Carcinoma That Responded to Combination Therapy Comprising Irinotecan and Cisplatin].

We report a case of resected esophagealcancer that responded wellto first-line combination therapy comprising irinotecan and cisplatin. The patient was a 71-year-old woman being treated for liver cirrhosis. She was admitted to our hospital in April 2015 because of dysphasia. Endoscopic examination revealed a tumor in the mid-thoracic esophagus, which was diagnosed as an endocrine cell carcinoma following pathological examination. Contrast-enhanced computed tomography and positron emission tomography did not show lymph node or distant metastases. She was treated with irinotecan and cisplatin combination therapy. After 6 courses of treatment, the tumor size had remarkably reduced. Subsequently, we performed subtotal esophagectomy and gastric tube reconstruction through the retroposterior mediastinalroute and the histologicaleffect was reported as a partial response. No viable tumor cells were observed in the extracted lymph nodes. However, bone metastasis and lymph node swelling occurred after 4 months. She received other therapeutic regimens, such as etoposide and carboplatin combination therapy. However, the tumor gradually progressed, and she died 18 months after the first treatment. Irinotecan and cisplatin combination therapy is a possible option for the management of esophageal endocrine cell carcinoma as a first-line treatment.

[A Case of Effective Chemoradiotherapy Using mFOLFOX6 for Locally Advanced Rectal Cancer].

We report a case of locally advanced rectal cancer, treated effectively with chemotherapy consisting of mFOLFOX6 combined with radiotherapy. A 63-year-old man was admitted to our hospital in March 2012 for diarrhea and anal and perineal pain. Advanced rectal cancer with invasion ofthe right perineum was diagnosed based on computer tomography(CT) findings. Surgery was performed; however, the rectal cancer was unresectable. A sigmoid colostomy was performed, and a central venous port was implanted. In April 2012, the patient was treated with chemotherapy using 3 courses ofmFOLFOX6 and concurrent radiotherapy. Radiotherapy at 2 Gy/day was administered 25 times(total dose, 50 Gy). After chemoradiotherapy, the patient underwent 3 courses ofmFOLFOX6 as an additional therapy. By June 2012, CT showed resolution ofthe tumor in the right perineum and a marked decrease in the size ofthe primary rectal cancer. Because the patient refused surgery, we started treatment with combination chemotherapy using oral S-1 and intravenous CPT-11 in August 2012. After 18 courses, the treatment was changed to oral administration ofS -1 alone, which was continued for 1 year. The patient remained well without recurrence for 54 months since the original diagnosis. Therefore, chemoradiotherapy with mFOLFOX6 is a possible option for the management of advanced rectal cancer.

[A Case of Resected Advanced Esophageal Cancer That Responded to Combination Therapy Comprising Docetaxel, Cisplatin, and 5-Fluorouracil].

We report a case of resected advanced esophagealcancer that responded wellto first-line combination therapy with docetaxel, cisplatin, and 5-fluorouracil(DCF therapy). A 72-year-old man was admitted to our hospital in January 2013 because of dysphagia. On the basis of the computed tomography(CT)and gastroendoscopy findings, he was diagnosed with advanced esophagealcancer with lymph node metastasis. The patient was treated with DCF therapy. After 2 courses of treatment, the primary tumor and lymph node metastasis were reduced on CT. After 3 courses of treatment, we performed subtotalesophagectomy and gastric tube reconstruction through the retroposterior mediastinalroute. No residualcancer cells were found in the esophagus or lymph nodes. The patient subsequently received oral administration of tegafur-uracilal one for 24 months. The post-operative course was uneventful, and there was no detectable lymph node metastasis 42 months after the originaldiagnosis. Therefore, DCF therapy is a possible option for the management of advanced esophagealcancer.

Preoperative Biliary Drainage in Cases of Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Chemotherapy and Surgery.

Objective. To elucidate the optimum preoperative biliary drainage method for patients with pancreatic cancer treated with neoadjuvant chemotherapy (NAC). Material and Methods. From January 2010 through December 2014, 20 patients with borderline resectable pancreatic cancer underwent preoperative biliary drainage and NAC with a plastic or metallic stent and received NAC at Hiroshima University Hospital. We retrospectively analyzed delayed NAC and complication rates due to biliary drainage, effect of stent type on perioperative factors, and hospitalization costs from diagnosis to surgery. Results. There were 11 cases of preoperative biliary drainage with plastic stents and nine metallic stents. The median age was 64.5 years; delayed NAC occurred in 9 cases with plastic stent and 1 case with metallic stent (p = 0.01). The complication rates due to biliary drainage were 0% (0/9) with metallic stents and 72.7% (8/11) with plastic stents (p = 0.01). Cumulative rates of complications determined with the Kaplan-Meier method on day 90 were 60% with plastic stents and 0% with metallic stents (log-rank test, p = 0.012). There were no significant differences between group in perioperative factors or hospitalization costs from diagnosis to surgery. Conclusions. Metallic stent implantation may be effective for preoperative biliary drainage for pancreatic cancer treated with NAC.

A comparison of 4-Fr with 5-Fr endoscopic nasopancreatic drainage catheters: A randomized, controlled trial.

BACKGROUND AND AIM: Although endoscopic nasopancreatic drainage (ENPD) is useful for collecting samples for pancreatic juice cytology and for treating leakage of pancreatic juice and occlusive pancreatitis, placement of the ENPD catheter is associated with complications such as post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We investigated whether an ENPD catheter with a smaller diameter could reduce the incidence of complications. METHODS: Patients requiring placement of an ENPD catheter (n = 254) were enrolled and randomly assigned to one of two catheter-size groups: the 4-Fr group or the 5-Fr group. The incidence of PEP, cholangitis, and spontaneous catheter displacement and the suitability of pancreatic juice cytology samples were compared between groups. In addition, univariate and multivariate analyses were conducted on factors associated with PEP. RESULTS: The incidence of PEP was significantly lower in the 4-Fr group compared with the 5-Fr group (4.1% vs 12.4%, respectively; P = 0.021). The rate of cholangitis and spontaneous catheter displacement and the suitability of pancreatic juice cytology samples did not differ between groups. Multivariate analysis revealed that the risk of PEP was 3.7 times higher when using a 5-Fr catheter than when using a 4-Fr catheter (P = 0.019). In addition, the risk of PEP was 4.1 times higher in patients with an intraductal papillary mucinous neoplasm than in those without (P = 0.0049) and 4.6 times higher in patients aged <65 than in those aged ≥65 (P = 0.0033). CONCLUSIONS: A 4-Fr catheter is as useful as a 5-Fr catheter and is associated with a significantly lower incidence of PEP.

Evaluation of antibiotic use to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis and cholangitis.

BACKGROUND/AIMS: The purpose of this study was to evaluate the relationship between prophylactic antibiotic use and complications following endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: We retrospectively evaluated 605 consecutive patients who underwent ERCP in our hospital between September 2009 and November 2011. The antibiotic group included patients who underwent their procedure before October 2010, while the control group included patients after October 1, 2010, who did not receive antibiotics. We compared the incidence of postoperative pancreatitis and cholangitis between the groups. RESULTS: There were no significant differences in the backgrounds of the 304 control and the 301 antibiotic-treated patients. The incidence of post-ERCP pancreatitis was 4.9% in the control group and 4.3% in the antibiotic group (p = 0.72). The incidence of postoperative cholangitis was 2.0% in the control group and 1.7% in the antibiotic group (p = 0.99). Choledocholithiasis, pancreatic duct injection, and female gender were detected as significant risk factors for postoperative pancreatitis by multivariate analysis; sclerosing cholangitis and incomplete biliary drainage were significant risk factors for postoperative cholangitis. Even in cases with these risk factors, prophylactic antibiotic use did not influence the incidence of pancreatitis or cholangitis. CONCLUSION: Prophylactic antibiotics do not reduce the incidence of either pancreatitis or cholangitis following ERCP.

Occupational Radiation Exposure during Endoscopic Retrograde Cholangiopancreatography and Usefulness of Radiation Protective Curtains.

Objective. To evaluate the effectiveness of radiation protective curtains in reducing the occupational radiation exposure of medical personnel. Methods. We studied medical staff members who had assisted in 80 consecutive therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures. Use of radiation protective curtains mounted to the X-ray tube was determined randomly for each procedure, and radiation doses were measured with electronic pocket dosimeters placed outside the protective apron. Results. When protective curtains were not used, the mean radiation doses to endoscopists, first assistants, second assistants, and nurses were 340.9, 27.5, 45.3, and 33.1 µSv, respectively; doses decreased to 42.6, 4.2, 13.1, and 10.6 µSv, respectively, when protective curtains were used (P < 0.01). When the patient had to be restrained during ERCP (n = 8), the radiation dose to second assistants without protective curtains increased by a factor of 9.95 (P < 0.01) relative to cases in which restraint was not required. Conclusions. During ERCP, not only endoscopists, but also assistants and nurses were exposed to high doses of radiation. Radiation exposure to staff members during ERCP was reduced with the use of protective curtains.

[Hepatic artery pseudoaneurysm after endoscopic biliary stenting for pancreatic cancer].

A man in his sixties presented to our hospital with obstructive jaundice and was diagnosed with inoperable pancreatic cancer. Chemoradiotherapy was initiated, and an expandable metallic stent was inserted endoscopically to drain the biliary system. Six months later, he was referred to our hospital with 1-week history of epigastric pain and obstructive jaundice. On admission for further evaluation, he experienced hematemesis and went into severe shock. Upper gastrointestinal endoscopy and endoscopic retrograde cholangiopancreatography showed active bleeding from the duodenal papilla. Therefore, we performed endoscopic nasobiliary drainage (ENBD). On day 4, blood was detected in the ENBD tube, and the patient again experienced hematemesis. Emergent enhanced computed tomography revealed a right hepatic arterial aneurysm that had likely ruptured and caused the hemobilia. The aneurysm was successfully embolized, and the patient was discharged on hospital day 21.

Timing of radiological improvement after steroid therapy in patients with autoimmune pancreatitis.

OBJECTIVE: We retrospectively studied the timing of radiological improvement after steroid therapy in patients with autoimmune pancreatitis (AIP). MATERIAL AND METHODS: Patients with AIP (n = 31) received steroids followed by diagnostic imaging within 1 month. Pancreatic swelling, pancreatic and bile duct features, and apparent diffusion coefficient (ADC) were compared before and after treatment. The period from treatment initiation to evaluation was divided into five phases: early phase (days 3-5), week 1 (days 6 and 7), week 2 (days 8-14), week 3 (days 15-21), and week 4 (days 22-28). Five gastroenterologists evaluated pancreatic swelling and duct features (good/intermediate/no response), and the "good response" rate (response rate) was calculated for each phase. In addition, pancreatic volumes were measured with a 3D workstation before and after treatment, and the percentage change in volume was calculated. ADC values were calculated in 14 patients. RESULTS: The median ratio of pancreatic volume after relative to before treatment was 0.89, 0.79, 0.67, 0.59, and 0.47 for early phase, week 1, week 2, week 3, and week 4, respectively. The response rate of the pancreatic swelling was 37.5%, 57.1%, 83.3%, 100%, and 100%; response rate of the pancreatic duct was 0%, 20%, 75%, 75% and 100%; and response rate of the bile duct was 0%, 66.7%, 83.3%, 100%, and 80%. The ADC increased after treatment in all 14 patients, including the 7 patients evaluated in the early phase. CONCLUSIONS: Evaluation of pancreatic swelling and duct features is recommended in week 2 and thereafter. The ADC increased soon after treatment initiation, suggesting its usefulness for evaluating early treatment responses.

Comparative study of 4 Fr versus 6 Fr nasobiliary drainage catheters: a randomized, controlled trial.

BACKGROUND AND AIM: Despite the benefits of endoscopic nasobiliary drainage (NBD) in endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) and nose/throat discomfort can result. We aimed to determine whether the use of a smaller catheter alleviates these complications. METHOD: A randomized, controlled trial at a tertiary care center compared 4 Fr and 6 Fr NBD catheters; 165 ERCP patients with naïve papillae were randomly assigned to a catheter-size group. RESULTS: The prevalence of PEP was significantly lower in the 4 Fr group (3.7%; 3/82) than in the 6 Fr group (15.7%; 13/83; P = 0.019). No spontaneous catheter displacement occurred within 24 h. Discomfort visual analog scores were 2.6 and 4.3 in the 4 Fr and 6 Fr groups, respectively (P = 0.0048) on procedure day; on the following day, the scores were 2.3 and 3.6 (P = 0.028). Bile output was 16.3 mL/h and 21.4 mL/h in the 4 Fr and 6 Fr groups (P = 0.051). On obstructive jaundice subgroup analysis, bile drainage was 19.2 mL/h and 22.1 mL/h in the 4 Fr and 6 Fr groups (P = 0.40). The 4 Fr group required 5.6 days to reduce bilirubin levels versus 6.1 days in the 6 Fr group (P = 0.51). CONCLUSIONS: In patients with naïve papillae, lower rates of PEP and less nose/throat discomfort are associated with the use of 4 Fr NBD catheters. In patients with obstructive jaundice, 4 Fr and 6 Fr catheters are comparable with regard to bile output and bilirubin level reduction.

Characteristic Features of Cholangiocarcinoma Complicating Primary Sclerosing Cholangitis.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is often complicated by cholangiocarcinoma (CCA); thus, early detection of CCA is an important way to improve PSC prognosis. METHODOLOGY: In a retrospective study, 23 cases of PSC were included. Seven cases were complicated by CCA (CCA group) and 16 cases were not (control group). Blood examinations, bile duct imagings from direct cholangiography, intraductal ultrasonography (IDUS) findings and pathological diagnosis results (bile juice cytology, brush cytology, and forceps biopsy) were referenced. RESULTS: Blood examinations showed that serum carbohydrate antigen 19-9 (CA19-9), total bilirubin, and aspartate aminotransferase were significantly higher in the CCA group, whereas cholangiography showed that the dominant stricture was significantly longer in the CCA group. No significant difference in the IDUS findings was observed between the 2 groups. Cholangioscopy enabled CCA diagnosis via identification of the papillary mucosa in sites other than the stricture. Forceps biopsy was the most useful pathological diagnostic technique, with a sensitivity of 86% and a specificity of 100%. CONCLUSIONS: The CA19-9 level and bile duct stricture morphology were useful for diagnosing CCA complicating PSC. Aggressive performance of cholangioscopy and pathological diagnostic techniques, such as brush cytology and forceps biopsy, are essential for identification.

Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: ιmplications for cholangiocarcinogenesis.

Cholangiocarcinoma (CCA) occurs frequently in primary sclerosing cholangitis (PSC). Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) induced by inflammation are believed to mediate prostaglandin E2 (PGE2) production thereby promoting carcinogenesis. Their expression in PSC-associated CCA tissues and non-neoplastic bile duct epithelial cells (BDECs) in PSC was investigated. COX-2 and mPGES-1 levels in 15 PSC patients (7 with CCA) were scored using immunohistochemical staining. The results were compared with those obtained in CCA tissues and non-neoplastic BDECs (controls) of 15 sporadic CCA patients. Non-neoplastic BDECs from large and small bile ducts were investigated separately. The mRNA expression levels of COX-2 and mPGES-1 in CCA tissues were analyzed by quantitative polymerase chain reaction. Ki-67 immunostaining was performed to evaluate cell proliferation. COX-2 was strongly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC. This expression was significantly upregulated in both compared with sporadic CCA tissues and non-neoplastic BDECs in sporadic CCA (both P<0.01). mPGES-1 was expressed at moderate to strong levels in PSC. Compared with controls, the expression was significantly higher in non-neoplastic small BDECs (P<0.01). COX-2 mRNA levels were significantly higher in PSC-associated tissues than in sporadic CCA tissues (P<0.01). Conversely, no differences were observed in mPGES-1 mRNA levels. Ki-67 labeling indices were higher in PSC-associated CCA tissues and non-neoplastic BDECs in PSC than in controls. In conclusion, COX-2 and mPGES-1 were highly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC, suggesting the involvement of COX-2 and mPGES-1 in cholangiocarcinogenesis.

[Malignant phyllodes tumor metastatic to the pancreas: a case report].

A woman in her 50s was admitted with obstructive jaundice due to a pancreatic mass. She had a history of a right breast phyllodes tumor treated with mastectomy 3 years previously. Diagnostic imaging (endoscopic ultrasonography (EUS), CT, and MRI) demonstrated a well-demarcated mass in the pancreatic head. EUS-FNA showed spindle shaped tumor cells. The pancreaticoduodenectomy specimen showed a malignant spindle cell tumor consistent with a metastatic malignant phyllodes tumor. In addition, immunohistochemical staining demonstrated that the staining pattern of pancreatic tumor was similar to that of the breast phyllodes tumor. Pancreatic metastases from breast phyllodes tumors have rarely been reported in the literature.

A case of double gallbladder with adenocarcinoma arising from the left hepatic duct: a case report and review of the literature.

Double gallbladder is a rare congenital biliary anomaly, but an accessory gallbladder arising from the left hepatic duct is a more remarkably rare congenital anomaly. We report a case of double gallbladder with adenocarcinoma and gallstones, which was preoperatively diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) and then confirmed by open laparotomy. A review of the literature is presented.